Effects of colchicine on the maximum biliary excretion of cholephilic compounds in rats

Autor: Hidetaka Tachizawa, Hajime Takikawa, Naoyo Sano
Rok vydání: 2004
Předmět:
Zdroj: Journal of Gastroenterology and Hepatology. 19:1016-1022
ISSN: 1440-1746
0815-9319
Popis: Background and Aim: Colchicine, an inhibitor of intracellular vesicular transport, has been reported to inhibit the biliary excretion of bile acids and organic anions, but the previous findings are controversial. In order to systematically evaluate the effect of colchicine on the biliary excretion of cholephilic compounds, we studied the effect of colchicine on the biliary excretion of substrates of various canalicular transporters, which were administered at or above the excretory maximum in rats. Methods: Substrates of various canalicular adenosine triphosphate-binding-cassette transporters were infused at or above the rate of maximum excretion into rats, and the effect of colchicine (0.2 mg/100 g), which was intraperitoneally injected 3 h before, on the biliary excretion was studied. Furthermore, the effect of tauroursodeoxycholate (TUDC) co-infusion on the biliary excretion of taurocholate (TC) after colchicine treatment was also studied. Results: The biliary excretion of TC and cholate administered at the rate of 1 µmol/min/100 g was markedly inhibited by colchicine, whereas that of TUDC was not inhibited even with the infusion rate of 2 µmol/min/100 g. TUDC co-infusion at the rate of 1 µmol/min/100 g increased the biliary excretion of TC (1 µmol/min/100 g), which was decreased by the colchicine pretreatment. The biliary excretory maximum of taurolithocholate-sulfate and sulfobromophthalein, substrates of the multidrug resistance protein 2, of erythromycin, a substrate of the P-glycoprotein, and of indocyanine green were not affected by colchicine. Conclusions: The different excretory maximums of TC and TUDC and the different effect of colchicine on the excretion of these bile acids are considered to be a result of different regulatory mechanisms of vesicular targeting of the bile salt export pump to the canalicular membrane by these bile acid conjugates. The vesicular targeting of the multidrug resistance protein 2 and the P-glycoprotein to the canalicular membrane is considered to be colchicine insensitive in the absence of bile acid coadministration.
Databáze: OpenAIRE
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